Antimicrobial use and outcomes in patients with multidrug-resistant and pansusceptible Salmonella Newport infections, 2002-2003.

Multidrug-resistant Salmonella Newport with decreased susceptibility to ceftriaxone (MDR-AmpC) is becoming increasingly common in its food animal reservoirs and in humans. Few data exist on rates of antimicrobial use or differences in clinical outcomes in persons infected with MDR-AmpC or other Salmonella strains. We conducted a case-comparison analysis of data from a multistate population-based case-control study to identify antimicrobial treatment choices and differences in clinical outcomes in those infected with MDRAmpC compared to pansusceptible S. Newport. Of isolates from 215 laboratory-confirmed S. Newport cases, 54 (25%) were MDR-AmpC, 146 (68%) were pansusceptible, and 15 (7%) had other resistance patterns; 146 (68%) patients with S. Newport were treated with antimicrobial agents and 66 (33%) were hospitalized. Over two-thirds of cases at low-risk for serious complications received antimicrobial therapy, most commonly with fluoroquinolones, to which this strain was susceptible. There were no significant differences in symptoms, hospitalization, duration of illness, or other outcomes between the persons infected with MDR-AmpC and pansusceptible S. Newport. Although currently prevalent MDR-AmpC S. Newport strains remains susceptible to the antimicrobial most commonly prescribed for it, continued efforts to reduce unnecessary use of antimicrobial agents in food animals and humans are critical to prevent further development of resistance to quinolones and cephalosporins, which is likely to lead to substantial adverse outcomes.

Neurons with object-centered spatial selectivity in macaque SEF: do they represent locations or rules?

In macaque monkeys performing a task that requires eye movements to the leftmost or rightmost of two dots in a horizontal array, some neurons in the supplementary eye field (SEF) fire differentially according to which side of the array is the target regardless of the array's location on the screen. We refer to these neurons as exhibiting selectivity for object-centered location. This form of selectivity might arise from involvement of the neurons in either of two processes: representing the locations of targets or representing the rules by which targets are selected. To distinguish between these possibilities, we monitored neuronal activity in the SEF of two monkeys performing a task that required the selection of targets by either an object-centered spatial rule or a color rule. On each trial, a sample array consisting of two side-by-side dots appeared; then a cue flashed on one dot; then the display vanished and a delay ensued. Next a target array consisting of two side-by-side dots appeared at an unpredictable location and another delay ensued; finally the monkey had to make an eye movement to one of the target dots. On some trials, the monkey had to select the dot on the same side as the cue (right or left). On other trials, he had to select the target of the same color as the cue (red or green). Neuronal activity robustly encoded the object-centered locations first of the cue and then of the target regardless of the whether the monkey was following a rule based on object-centered location or color. Neuronal activity was at most weakly affected by the type of rule the monkey was following (object-centered-location or color) or by the color of the cue and target (red or green). On trials involving a color rule, neuronal activity was moderately enhanced when the cue and target appeared on opposite sides of their respective arrays. We conclude that the general function of SEF neurons selective for object-centered location is to represent where the cue and target are in their respective arrays rather than to represent the rule for target selection.

Statistical analysis of temporal evolution in single-neuron firing rates.

A fundamental methodology in neurophysiology involves recording the electrical signals associated with individual neurons within brains of awake behaving animals. Traditional statistical analyses have relied mainly on mean firing rates over some epoch (often several hundred milliseconds) that are compared across experimental conditions by analysis of variance. Often, however, the time course of the neuronal firing patterns is of interest, and a more refined procedure can produce substantial additional information. In this paper we compare neuronal firing in the supplementary eye field of a macaque monkey across two experimental conditions. We take the electrical discharges, or 'spikes', to be arrivals in a inhomogeneous Poisson process and then model the firing intensity function using both a simple parametric form and more flexible splines. Our main interest is in making inferences about certain characteristics of the intensity, including the timing of the maximal firing rate. We examine data from 84 neurons individually and also combine results into a hierarchical model. We use Bayesian estimation methods and frequentist significance tests based on a nonparametric bootstrap procedure. We are thereby able to conclude that a substantial fraction of the neurons exhibit important temporal differences in firing intensity across the two conditions, and we quantify the effect across the population of neurons.

Neuronal activity related to rule and conflict in macaque supplementary eye field.

Neuronal activity in macaque supplementary eye field (SEF) is enhanced during performance of the antisaccade task. This could be related to the selection of targets by a difficult rule (move to a location diametrically opposite the cue) or to conflict between the automatic tendency to look at the cue and the voluntary intention to look away. To distinguish between rule- and conflict-based mechanisms of enhancement, we monitored neuronal activity in the SEF during performance of a delayed response task in which monkeys selected saccade targets in response to peripheral visual cues. In spatial trials, the monkey had to select as target the location marked by the cue. In color trials, the monkey had to select as target the location associated with the color of the cue. 'Color-congruent' trials resembled spatial trials in that saccades were directed to the location occupied by the cue. Nevertheless, many SEF neurons were sensitive to the rule being used, with the majority firing more strongly under the color-rule condition. 'Color-incongruent' trials resembled 'color-congruent' trials in that a color rule guided target selection. Nevertheless, many SEF neurons were sensitive to the spatial relation between cue and saccade, with the majority firing more strongly on trials in which they were incongruent. We conclude that neuronal activity in the SEF is enhanced in connection both with the use of a more difficult rule and with conflict.